title: The dyslexia-associated gene DCDC2 is required for spike-timing precision in mouse neocortex.
abstract: BACKGROUND
  Variants in dyslexia-associated genes, including DCDC2, have been linked to altered neocortical activation, suggesting that dyslexia associated genes might play as yet unspecified roles in neuronal physiology.
  
  
  METHODS
  Whole-cell patch clamp recordings were used to compare the electrophysiological properties of regular spiking pyramidal neurons of neocortex in Dcdc2 knockout (KO) and wild-type mice. Ribonucleic acid sequencing and reverse transcriptase polymerase chain reaction were performed to identify and characterize changes in gene expression in Dcdc2 KOs.
  
  
  RESULTS
  Neurons in KOs showed increased excitability and decreased temporal precision in action potential firing. The RNA sequencing screen revealed that the N-methyl-D-aspartate receptor (NMDAR) subunit Grin2B was elevated in Dcdc2 KOs, and an electrophysiological assessment confirmed a functional increase in spontaneous NMDAR-mediated activity. Remarkably, the decreased action potential temporal precision could be restored in mutants by treatment with either the NMDAR antagonist (2R)-amino-5-phosphonovaleric acid or the NMDAR 2B subunit-specific antagonist Ro 25-6981.
  
  
  CONCLUSIONS
  These results link the function of the dyslexia-associated gene Dcdc2 to spike timing through activity of NMDAR.
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut.
authors.forename: Alicia
authors.initials: A
authors.lastname: Che
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Girgenti
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut. Electronic address: Joseph.LoTurco@uconn.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: LoTurco
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004410:Dyslexia / Q000235:genetics; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015870:Gene Expression; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008839:Microelectrodes; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D019579:Neocortex / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D046509:Tissue Culture Techniques
chemical_list: C570668:DCDC2 protein, mouse; D018691:Excitatory Amino Acid Antagonists; D008869:Microtubule-Associated Proteins; C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D015763:2-Amino-5-phosphonovalerate
keywords: Dcdc2; Grin2B; dyslexia; excitability; neocortex; spike-time precision